| 1. |
- Su, Zhan, et al.
(författare)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Abacan, MaryAnn, et al.
(författare)
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The Global State of the Genetic Counseling Profession
- 2019
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Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 27:2, s. 183-197
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Forskningsöversikt (refereegranskat)abstract
- The profession of genetic counseling (also called genetic counselling in many countries) began nearly 50 years ago in the United States, and has grown internationally in the past 30 years. While there have been many papers describing the profession of genetic counseling in individual countries or regions, data remains incomplete and has been published in diverse journals with limited access. As a result of the 2016 Transnational Alliance of Genetic Counseling (TAGC) conference in Barcelona, Spain, and the 2017 World Congress of Genetic Counselling in the UK, we endeavor to describe as fully as possible the global state of genetic counseling as a profession. We estimate that in 2018 there are nearly 7000 genetic counselors with the profession established or developing in no less than 28 countries.
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| 7. |
- Bansal, Sheel, et al.
(författare)
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Practical Guide to Measuring Wetland Carbon Pools and Fluxes
- 2023
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Ingår i: Wetlands (Wilmington, N.C.). - : SPRINGER. - 0277-5212 .- 1943-6246. ; 43:8
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Forskningsöversikt (refereegranskat)abstract
- Wetlands cover a small portion of the world, but have disproportionate influence on global carbon (C) sequestration, carbon dioxide and methane emissions, and aquatic C fluxes. However, the underlying biogeochemical processes that affect wetland C pools and fluxes are complex and dynamic, making measurements of wetland C challenging. Over decades of research, many observational, experimental, and analytical approaches have been developed to understand and quantify pools and fluxes of wetland C. Sampling approaches range in their representation of wetland C from short to long timeframes and local to landscape spatial scales. This review summarizes common and cutting-edge methodological approaches for quantifying wetland C pools and fluxes. We first define each of the major C pools and fluxes and provide rationale for their importance to wetland C dynamics. For each approach, we clarify what component of wetland C is measured and its spatial and temporal representativeness and constraints. We describe practical considerations for each approach, such as where and when an approach is typically used, who can conduct the measurements (expertise, training requirements), and how approaches are conducted, including considerations on equipment complexity and costs. Finally, we review key covariates and ancillary measurements that enhance the interpretation of findings and facilitate model development. The protocols that we describe to measure soil, water, vegetation, and gases are also relevant for related disciplines such as ecology. Improved quality and consistency of data collection and reporting across studies will help reduce global uncertainties and develop management strategies to use wetlands as nature-based climate solutions.
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| 8. |
- Barbera, Mariagnese, et al.
(författare)
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A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol
- 2024
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central Ltd. - 1758-9193. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Combining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer’s Disease and emerging evidence of its potential neuro-protective effects (e.g. vascular, metabolic, anti-senescence). MET-FINGER aims to test a FINGER 2.0 multimodal intervention, combining an updated FINGER multidomain lifestyle intervention with metformin, where appropriate, in an APOE ε4-enriched population of older adults (60–79 years) at increased risk of dementia.Methods: MET-FINGER is an international randomised, controlled, parallel-group, phase-IIb proof-of-concept clinical trial, where metformin is included through a trial-within-trial design. 600 participants will be recruited at three sites (UK, Finland, Sweden). Participants at increased risk of dementia based on vascular risk factors and cognitive screening, will be first randomised to the FINGER 2.0 intervention (lifestyle + metformin if eligible; active arm) or to receive regular health advice (control arm). Participants allocated to the FINGER 2.0 intervention group at risk indicators of T2D will be additionally randomised to receive metformin (2000 mg/day or 1000 mg/day) or placebo. The study duration is 2 years. The changes in global cognition (primary outcome, using a Neuropsychological Test Battery), memory, executive function, and processing speed cognitive domains; functional status; lifestyle, vascular, metabolic, and other dementia-related risk factors (secondary outcomes), will be compared between the FINGER 2.0 intervention and the control arm. The feasibility, potential interaction (between-groups differences in healthy lifestyle changes), and disease-modifying effects of the lifestyle-metformin combination will be exploratory outcomes. The lifestyle intervention is adapted from the original FINGER trial (diet, physical activity, cognitive training, monitoring of cardiovascular/metabolic risk factors, social interaction) to be consistently delivered in three countries. Metformin is administered as Glucophage®XR/SR 500, (500 mg oral tablets). The metformin/placebo treatment will be double blinded. Conclusion: MET-FINGER is the first trial combining a multimodal lifestyle intervention with a putative repurposed disease-modifying drug for cognitive impairment prevention. Although preliminary, its findings will provide crucial information for innovative precision prevention strategies and form the basis for a larger phase-III trial design and future research in this field.
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| 9. |
- Bray, Lucy, et al.
(författare)
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"People play it down and tell me it can't kill people, but I know people are dying each day". Children's health literacy relating to a global pandemic (COVID-19); an international cross sectional study.
- 2021
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine aspects of children's health literacy; the information sources they were accessing, their information preferences, their perceived understanding of and their reported information needs in relation to COVID-19. An online survey for children aged 7-12 years of age and parent/caregivers from the UK, Sweden, Brazil, Spain, Canada and Australia was conducted between 6th of April and the 1st of June 2020. The surveys included demographic questions and both closed and open questions focussing on access to and understanding of COVID-19 information. Descriptive statistics and qualitative content analysis procedures were conducted. The findings show that parents are the main source of information for children during the pandemic in most countries (89%, n = 347), except in Sweden where school was the main source of information. However, in many cases parents chose to shield, filter or adapt their child's access to information about COVID-19, especially in relation to the death rates within each country. Despite this, children in this study reported knowing that COVID-19 was deadly and spreads quickly. This paper argues for a community rather than individual approach to addressing children's health literacy needs during a pandemic.
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| 10. |
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| 11. |
- Bunting, M. J., et al.
(författare)
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Palynological perspectives on vegetation survey: a critical step for model-based reconstruction of Quaternary land cover
- 2013
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 82, s. 41-55
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Tidskriftsartikel (refereegranskat)abstract
- 1. Quantitative reconstruction of past vegetation distribution and abundance from sedimentary pollen records provides an important baseline for understanding long term ecosystem dynamics and for the calibration of earth system process models such as regional-scale climate models, widely used to predict future environmental change. Most current approaches assume that the amount of pollen produced by each vegetation type, usually expressed as a relative pollen productivity term, is constant in space and time. 2. Estimates of relative pollen productivity can be extracted from extended R-value analysis (Parsons and Prentice, 1981) using comparisons between pollen assemblages deposited into sedimentary contexts, such as moss polsters, and measurements of the present day vegetation cover around the sampled location. Vegetation survey method has been shown to have a profound effect on estimates of model parameters (Bunting and Hjelle, 2010), therefore a standard method is an essential pre-requisite for testing some of the key assumptions of pollen-based reconstruction of past vegetation; such as the assumption that relative pollen productivity is effectively constant in space and time within a region or biome. 3. This paper systematically reviews the assumptions and methodology underlying current models of pollen dispersal and deposition, and thereby identifies the key characteristics of an effective vegetation survey method for estimating relative pollen productivity in a range of landscape contexts. 4. It then presents the methodology used in a current research project, developed during a practitioner workshop. The method selected is pragmatic, designed to be replicable by different research groups, usable in a wide range of habitats, and requiring minimum effort to collect adequate data for model calibration rather than representing some ideal or required approach. Using this common methodology will allow project members to collect multiple measurements of relative pollen productivity for major plant taxa from several northern European locations in order to test the assumption of uniformity of these values within the climatic range of the main taxa recorded in pollen records from the region. (C) 2013 Elsevier Ltd. All rights reserved.
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| 12. |
- Bunting, M J, et al.
(författare)
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Vegetation structure and pollen source area
- 2004
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Ingår i: The Holocene. - : SAGE Publications. - 0959-6836 .- 1477-0911. ; 14:5, s. 651-660
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we use a simulation approach to explore the effect of variation in taxon parameters and landscape patterning on relevant source area of pollen. We use the Prentice-Sugita model, assume constant atmospheric conditions and basin morphology, and take a reductionist approach to explore the behaviour of pollen dispersal and deposition in a simple landscape scenario. Individual factors within the scenario (pollen fall speed, relative pollen productivity, size of basic unit in the landscape mosaic, patch size, rarity of individual taxa and overall number of taxa present in the landscape) are varied while all other parameters are kept constant, thus permitting exploration of the role of different components of the system. These simulations suggest that, for basins of given size under fixed atmospheric conditions, the relevant source area of pollen is primarily an expression of the patterning of the different vegetation elements within the landscape. This has important implications for the interpretation of palaeoecological records and reconstruction of past environments. Reconstruction, especially quantitative reconstruction, requires some estimate of past relevant source area of pollen. If, as our results suggest, vegetation patterning is an important determinant of this, then it must also be taken into account when attempting to reconstruct past vegetation communities.
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| 13. |
- Cruickshank, Tess, et al.
(författare)
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Circulating growth differentiation factor 15 is increased preceding preeclampsia diagnosis: Implications as a disease biomarker
- 2021
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 10:16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We investigated the biomarker potential of growth differentiation factor 15 (GDF-15), a stress response protein highly expressed in placenta, to predict preeclampsia. METHODS AND RESULTS: In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 controls, 41 developed preeclampsia), plasma concentrations of GDF-15 at 36 weeks’ gestation were significantly increased among those who developed preeclampsia (P<0.001), area under the receiver operating characteristic curves (AUC) of 0.66 and 0.71, respectively. In cohort 2 a ratio of sFlt-1/PlGF (a clinical biomarker for preeclampsia) had a sensitivity of 61.0% at 83.2% specificity to predict those who will develop preeclampsia (AUC of 0.79). A ratio of GDF-15×sFlt-1/PlGF yielded a sensitivity of 68.3% at 83.2% specificity (AUC of 0.82). GDF-15 was consistently elevated across a number of international cohorts: levels were higher in placenta and blood from women delivering <34 weeks’ gestation due to preterm preeclampsia in Melbourne, Australia; and in the blood at 26 to 32 weeks’ gestation among 57 women attending the Manchester Antenatal Vascular Service (MAViS, UK) who developed preeclampsia (P=0.0002), compared with 176 controls. In the Preeclampsia Obstetric adVerse Events biobank (PROVE, South Africa), plasma GDF-15 was significantly increased in women with preec-lampsia with severe features (P=0.02; n=14) compared to controls (n=14). CONCLUSIONS: We conclude circulating GDF-15 is elevated among women more likely to develop preeclampsia or diagnosed with the condition. It may have value as a clinical biomarker, including the potential to improve the sensitivity of sFlt-1/PlGF ratio.
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| 14. |
- Forsberg, Lars, et al.
(författare)
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Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers
- 2023
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Ingår i: Multiple Sclerosis Journal, Experimental, Translational and Clinical. - : SAGE Publications. - 2055-2173. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTo assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing-remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported. Materials and methodsData were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the United Kingdom (UK), including date of birth, sex, SP conversion year, visits with an Expanded Disability Status Scale (EDSS) score, MS onset and diagnosis date, relapses, and disease-modifying treatment (DMT) use. We included RRMS or SPMS patients with at least one visit between January 2017 and December 2019 if >= 18 years of age. We applied three objective methods: A set of SPMS clinical trial inclusion criteria ("EXPAND criteria") modified for a real-world evidence setting, a modified version of the MSBase algorithm, and a decision tree-based algorithm recently published. ResultsThe clinically assigned proportion of SPMS varied from 8.7% (Czechia) to 34.3% (UK). Objective classifiers estimated the proportion of SPMS from 15.1% (Germany by the EXPAND criteria) to 58.0% (UK by the decision tree method). Due to different requirements of number of EDSS scores, classifiers varied in the proportion they were able to classify; from 18% (UK by the MSBase algorithm) to 100% (the decision tree algorithm for all registries). Objectively classified SPMS patients were older, converted to SPMS later, had higher EDSS at index date and higher EDSS at conversion. More objectively classified SPMS were on DMTs compared to the clinically assigned. ConclusionSPMS appears to be systematically underdiagnosed in MS registries. Reclassified patients were more commonly on DMTs.
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| 15. |
- Gaillard, Marie-Jose, et al.
(författare)
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The use of modelling and simulation approach in reconstructing past landscapes from fossil pollen data: a review and results from the POLLANDCAL network
- 2008
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Ingår i: Vegetation History and Archaeobotany. - : Springer Science and Business Media LLC. - 0939-6314 .- 1617-6278. ; 17:5, s. 419-443
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Tidskriftsartikel (refereegranskat)abstract
- Information on past land cover in terms of absolute areas of different landscape units (forest, open land, pasture land, cultivated land, etc.) at local to regional scales is needed to test hypotheses and answer questions related to climate change (e.g. feedbacks effects of land-cover change), archaeological research, and nature conservancy (e.g. management strategy). The palaeoecological technique best suited to achieve quantitative reconstruction of past vegetation is pollen analysis. A simulation approach developed by Sugita (the computer model POLLSCAPE) which uses models based on the theory of pollen analysis is presented together with examples of application. POLLSCAPE has been adopted as the central tool for POLLANDCAL (POLlen/LANdscape CALibration), an international research network focusing on this topic. The theory behind models of the pollen-vegetation relationship and POLLSCAPE is reviewed. The two model outputs which receive greatest attention in this paper are the relevant source area of pollen (RSAP) and pollen loading in mires and lakes. Six examples of application of POLLSCAPE are presented, each of which explores a possible use of the POLLANDCAL tools and a means of validating or evaluating the models with empirical data. The landscape and vegetation factors influencing the size of the RSAP, the importance of pollen productivity estimates (PPEs) for the model outputs, the detection of small and rare patches of plant taxa in pollen records, and quantitative reconstructions of past vegetation and landscapes are discussed on the basis of these examples. The simulation approach is seen to be useful both for exploring different vegetation/landscape scenarios and for refuting hypotheses.
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| 16. |
- Gousia, Katarina, et al.
(författare)
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The impact of unemployment and non-standard forms of employment on the housing autonomy of young adults
- 2021
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Ingår i: Work, Employment and Society. - : Sage Publications. - 0950-0170 .- 1469-8722. ; 35:1, s. 157-177
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Tidskriftsartikel (refereegranskat)abstract
- Young people are facing challenges in transitioning to housing autonomy because of changes in labour market conditions in recent years. This article explores the effects of youth unemployment and non-standard employment on the likelihood of leaving the parental home. We adopt a dynamic modelling approach, and use data from a large longitudinal British survey covering the years 2009-2014. We find that unemployment and part-time work, but not the duration of the contract, have a negative effect on the likelihood of obtaining housing autonomy. We also find that past as well as anticipated unemployment have significant negative effects, which suggests that the decision about whether to move out depends on the individual’s longer-term labour market trajectory. The analysis also reveals gender differences in part-time work, but not in unemployment once we take into account unobserved time-invariant heterogeneity.
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| 17. |
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| 18. |
- Jaarsma, Tiny, et al.
(författare)
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Self-care research: How to grow the evidence base?
- 2020
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Ingår i: International Journal of Nursing Studies. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0020-7489 .- 1873-491X. ; 105
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Forskningsöversikt (refereegranskat)abstract
- Background and objective: The number of studies in the area of self-care is growing and international researchers are increasingly developing self-care interventions to improve outcomes of individual patients and communities. However, growth of the evidence is still slow due to challenges with designing and testing self-care interventions. In this article we address major methodological challenges with regard to the definition of self-care, use of theory, and research design, intended to provide guidance to researchers in this field. Method: During the inaugural conference of the International Center for Self-Care Research held in Rome, Italy in June 2019 we identified important issues in existing self-care research. Discussion and literature review lead to eight recommendation for future self-care research. Results: In preparation, begin with a theoretically sound definition of self-care. In planning the intervention, build on and extend previous studies. Use theory to develop self-care interventions and consider translational models to guide development, evaluation and implementation of complex self-care interventions. Employ a study design that fits the current phase and objectives of the research and measure self-care and related factors carefully. In reporting, describe the sample and setting sufficiently so that others can draw conclusions about generalizability and applicability to their practice and patient population. In interpretation, describe how the intervention is assumed to work (causal assumptions) and its key components. Conclusion: Our review of existing self-care research clearly illustrates that the recommendations we provide are needed if we are to substantially grow the evidence base supporting self-care. Embracing a core set of principles will allow us to build on each others work. Tweetable abstract: A core set of methodological principles is needed to substantially grow the evidence base supporting self-care. (C) 2020 The Authors. Published by Elsevier Ltd.
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| 19. |
- Jaarsma, Tiny, et al.
(författare)
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Self-care research: How to grow the evidence base? (reprint) (Reprinted from International Journal of Nursing Studies, vol 105, 103555, 2020)
- 2021
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Ingår i: International Journal of Nursing Studies. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0020-7489.
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Annan publikation (refereegranskat)abstract
- Background and objective: The number of studies in the area of self-care is growing and international researchers are increasingly developing self-care interventions to improve outcomes of individual patients and communities. However, growth of the evidence is still slow due to challenges with designing and testing self-care interventions. In this article we address major methodological challenges with regard to the definition of self-care, use of theory, and research design, intended to provide guidance to researchers in this field. Method: During the inaugural conference of the International Center for Self-Care Research held in Rome, Italy in June 2019 we identified important issues in existing self-care research. Discussion and literature review lead to eight recommendation for future self-care research. Results: In preparation, begin with a theoretically sound definition of self-care. In planning the intervention, build on and extend previous studies. Use theory to develop self-care interventions and consider translational models to guide development, evaluation and implementation of complex self-care interventions. Employ a study design that fits the current phase and objectives of the research and measure self-care and related factors carefully. In reporting, describe the sample and setting sufficiently so that others can draw conclusions about generalizability and applicability to their practice and patient population. In interpretation, describe how the intervention is assumed to work (causal assumptions) and its key components. Conclusion: Our review of existing self-care research clearly illustrates that the recommendations we provide are needed if we are to substantially grow the evidence base supporting self-care. Embracing a core set of principles will allow us to build on each others work. Tweetable abstract: A core set of methodological principles is needed to substantially grow the evidence base supporting self-care. (C) 2020 The Author(s). Published by Elsevier Ltd.
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| 20. |
- Kivipelto, Miia, et al.
(författare)
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World-Wide FINGERS Network : A global approach to risk reduction and prevention of dementia
- 2020
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:7, s. 1078-1094
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Tidskriftsartikel (refereegranskat)abstract
- Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.
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| 21. |
- Lennartson, Bengt, et al.
(författare)
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Low order sampled data H∞ control using the delta operator and LMIs
- 2004
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Ingår i: Decision and Control, 2004. CDC. 43rd IEEE Conference on. ; , s. 4479-4484
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Konferensbidrag (refereegranskat)abstract
- A procedure for H∞ optimization of low order controllers for discrete-time and sampled-data systems is presented in this paper. Generally, low order H∞ controllers may be achieved by solving bilinear matrix inequalities (BMIs). In this paper an iterative alternation between two LMIs gives a suboptimal solution. To avoid local minima in this search the initial controller is obtained by a frequency weighted controller reduction scheme, where the closed loop properties of a full order controller is taken into account. A minimal number of parameters in the state space realization of the controller also reduces the complexity and improves numerical robustness. The complete presentation is based on delta operator models, which shows a close relationship between the continuous- and discrete-time solutions. The sensitivity of the ordinary discrete-time shift operator LMI formulation to small sampling periods is also analyzed.
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| 22. |
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| 23. |
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| 24. |
- Lennartson, Bengt, et al.
(författare)
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Unified, periodic & sampled data H∞ control using the delta operator
- 2004
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Ingår i: Decision and Control, 2004. CDC. 43rd IEEE Conference on. ; , s. 2364-2369
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Konferensbidrag (refereegranskat)abstract
- A unified and general framework is presented for H∞ control of mixed continuous-time and discrete-time time-varying (periodic) systems. Using the delta operator, a close relationship is shown between the continuous- and discrete-time solutions. No assumptions are made on certain system matrices being zero or normalized, which makes the approach general and easy to apply. A combined continuous/discrete-time lifting procedure is shown to be useful, especially for ill-conditioned systems. This procedure together with the delta formalism results in a numerically robust design method concerning both short and long sampling periods for systems with W-conditioned dynamics, including widely spread eigenvalues.
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| 25. |
- Middleton, Anna, et al.
(författare)
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Attitudes of publics who are unwilling to donate DNA data for research.
- 2019
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 62:5, s. 316-323
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Tidskriftsartikel (refereegranskat)abstract
- With the use of genetic technology, researchers have the potential to inform medical diagnoses and treatment in actionable ways. Accurate variant interpretation is a necessary condition for the utility of genetic technology to unfold. This relies on the ability to access large genomic datasets so that comparisons can be made between variants of interest. This can only be successful if DNA and medical data are donated by large numbers of people to 'research', including clinical, non-profit and for-profit research initiatives, in order to be accessed by scientists and clinicians worldwide. The objective of the 'Your DNA, Your Say' global survey is to explore public attitudes, values and opinions towards willingness to donate and concerns regarding the donation of one's personal data for use by others. Using a representative sample of 8967 English-speaking publics from the UK, the USA, Canada and Australia, we explore the characteristics of people who are unwilling (n = 1426) to donate their DNA and medical information, together with an exploration of their reasons. Understanding this perspective is important for making sense of the interaction between science and society. It also helps to focus engagement initiatives on the issues of concern to some publics.
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| 26. |
- Middleton, Anna, et al.
(författare)
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Direct-to-consumer genetic testing : where and how does genetic counseling fit?
- 2017
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Ingår i: Personalized Medicine. - : FUTURE MEDICINE LTD. - 1741-0541 .- 1744-828X. ; 14:3, s. 249-257
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Tidskriftsartikel (refereegranskat)abstract
- Direct-to-consumer genetic testing for disease ranges from well-validated diagnostic and predictive tests to 'research' results conferring increased risks. While being targeted at public curious about their health, they are also marketed for use in reproductive decision-making or management of disease. By virtue of being 'direct-to-consumer' much of this testing bypasses traditional healthcare systems. We argue that direct-to-consumer genetic testing companies should make genetic counseling available, pre- as well as post-test. While we do not advocate that mandatory genetic counseling should gate-keep access to direct-to-consumer genetic testing, if the testing process has the potential to cause psychological distress, then companies have a responsibility to provide support and should not rely on traditional healthcare systems to pick up the pieces.
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| 27. |
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| 28. |
- Middleton, Anna, et al.
(författare)
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Global Public Perceptions of Genomic Data Sharing : What Shapes the Willingness to Donate DNA and Health Data?
- 2020
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 107:4, s. 743-752
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Tidskriftsartikel (refereegranskat)abstract
- Analyzing genomic data across populations is central to understanding the role of genetic factors in health and disease. Successful data sharing relies on public support, which requires attention to whether people around the world are willing to donate their data that are then subsequently shared with others for research. However, studies of such public perceptions are geographically limited and do not enable comparison. This paper presents results from a very large public survey on attitudes toward genomic data sharing. Data from 36,268 individuals across 22 countries (gathered in 15 languages) are presented. In general, publics across the world do not appear to be aware of, nor familiar with, the concepts of DNA, genetics, and genomics. Willingness to donate one's DNA and health data for research is relatively low, and trust in the process of data's being shared with multiple users (e.g., doctors, researchers, governments) is also low. Participants were most willing to donate DNA or health information for research when the recipient was specified as a medical doctor and least willing to donate when the recipient was a for-profit researcher. Those who were familiar with genetics and who were trusting of the users asking for data were more likely to be willing to donate. However, less than half of participants trusted more than one potential user of data, although this varied across countries. Genetic information was not uniformly seen as different from other forms of health information, but there was an association between seeing genetic information as special in some way compared to other health data and increased willingness to donate. The global perspective provided by our "Your DNA, Your Say" study is valuable for informing the development of international policy and practice for sharing genomic data. It highlights that the research community not only needs to be worthy of trust by the public, but also urgent steps need to be taken to authentically communicate why genomic research is necessary and how data donation, and subsequent sharing, is integral to this.
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| 29. |
- Middleton, Anna, et al.
(författare)
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Members of the public in the USA, UK, Canada and Australia expressing genetic exceptionalism say they are more willing to donate genomic data
- 2020
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 28:4, s. 424-434
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Tidskriftsartikel (refereegranskat)abstract
- Public acceptance is critical for sharing of genomic data at scale. This paper examines how acceptance of data sharing pertains to the perceived similarities and differences between DNA and other forms of personal data. It explores the perceptions of representative publics from the USA, Canada, the UK and Australia (n = 8967) towards the donation of DNA and health data. Fifty-two percent of this public held 'exceptionalist' views about genetics (i.e., believed DNA is different or 'special' compared to other types of medical information). This group was more likely to be familiar with or have had personal experience with genomics and to perceive DNA information as having personal as well as clinical and scientific value. Those with personal experience with genetics and genetic exceptionalist views were nearly six times more likely to be willing to donate their anonymous DNA and medical information for research than other respondents. Perceived harms from re-identification did not appear to dissuade publics from being willing to participate in research. The interplay between exceptionalist views about genetics and the personal, scientific and clinical value attributed to data would be a valuable focus for future research.
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| 30. |
- Middleton, Anna Won
(författare)
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Regulation of G2 phase and long-term consequences of DNA damage
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cell proliferation requires the accurate replication of DNA and equal segregation of replicated genes, important for maintaining the integrity of newly formed cells. At the centre of this process is a series of coordinated events termed ‘the cell cycle’, which ensures cell proliferation proceeds with high fidelity. Cell cycle regulation is driven by the activity of cyclin-dependent kinases (Cdks), which require binding to their regulatory subunit cyclin to become activated. However, the activity of Cdk is regulated by several different mechanisms. Transcription and degradation control mechanisms indirectly affect Cdk activity by modulating the expression of several regulatory proteins, including cyclins, while regulatory phosphorylation and dephosphorylation of cyclin-Cdk complexes provide direct control of Cdk activity. Such posttranslational modifications are frequently part of feedback loops, which fine-tune Cdk activity. These mechanisms collectively modulate successive activation of Cdks, and is responsible for timely phosphorylation of Cdk substrates to complete different phases of the cell cycle. This thesis concerns the regulation of G2 phase in the cell cycle, in relation to: 1) the effect of cyclin A2 localisation in G2 phase, 2) the changes in G2 phase regulation in a genetic disorder, and 3) the long-term consequences if G2 phase regulators are completely suppressed. Although Cdk activity is required for well-delineated cell cycle phase transitions, the spatiotemporal regulation of cyclin is important, as it provides unique substrate specificity and accessibility to the Cdk. Nevertheless, the exact mechanisms underlying the activation of cyclin-Cdk complexes remain largely elusive. The first part of this thesis investigates unknown mechanisms of mitotic kinase activation in G2 phase, by assessing the spatio-temporal regulation of cyclin A2 and its function in G2 phase. In paper I, we observe that nuclear cyclin A2 partially translocates to the cytoplasm at S/G2 phase transition. Interestingly, we reveal that cyclin A2-Cdk2 can initiate the activation of Plk1 through phosphorylation of Bora, but only cyclin A2 localised to the cytoplasm can interact with Bora and Plk1. We find no evidence that the change in localisation of cyclin A2 is involved in feedback loops in G2 phase. Thus, our study strongly supports the notion that cytoplasmic A2 functions as a trigger for the activation of mitotic kinases. Although the precise mechanism that changes the localisation of cyclin A2 to the cytoplasm requires further study, we show that cyclin A2 nuclear localisation until S/G2 phase transition is contributed, in part, by the association of cyclin A2 to chromatin during DNA replication. In addition, our work also reveals p21 can restrict cyclin A2 to the nucleus, especially after DNA damage. Together, paper I expands our understanding of the mechanisms of mitotic kinase activation in G2 phase, and identifies future areas of study to fill in our knowledge gaps of how cyclin A2 changes its cellular localisation. Cell cycle dysregulation has been implicated in many genetic diseases and disorders. This highlights the importance of understanding cell cycle regulation in certain disease settings. The second part of this thesis is dedicated to studying the role of a non-coding nuclear RNA gene, RMRP, that is mutated in the rare genetic disorder, cartilage-hair hypoplasia (CHH). CHH cells show proliferation defects, and studies on yeast suggest that RMRP could regulate the accumulation of cyclins. In paper II, we reveal RMRP has pleiotropic effects on several cell cycle regulatory genes, and the mutation of RMRP delays G2 phase progression to mitosis. Furthermore, our work finds evidence of possible impairment in the PI3K-Akt signalling pathway in CHH. These findings contribute to understanding the role of RMRP in cell cycle regulation, particularly in relation to CHH, and indicate a possible pathway for therapeutic interventions. The uncontrolled proliferation of cells with genomic instability can lead to the development of cancer. The cell cycle checkpoint is a mechanism that can restrict cell cycle progression in response to DNA damage and replication blocks. When checkpoint kinases are activated, signals are transmitted to a network of regulatory proteins that increase the inhibitory force and delay cell cycle progression. In the case of persistent DNA damage in G2 phase, p53 and p21- dependent premature activation of APC/CCdh1 mediates cell cycle termination by degrading all cell cycle regulatory proteins. While all these processes ensure genomic integrity, the mechanisms that allow escape from a checkpoint have been the focus of many studies, but whether cell cycle termination in G2 phase can be reversed remains unclear. Therefore, the last part of this thesis investigates the long-term consequences of DNA damage-induced cell cycle termination in G2 phase. Paper III shows that cells can re-initiate S phase after terminating the cell cycle in G2 phase. Interestingly, expression of p21 persists until cells re-initiate DNA replication and increases further once DNA re-replication is complete. This finding supports our observation of repeated cell cycle termination of re-replicated cells. Furthermore, re-replicated cells can progress to mitosis, which creates a heterogenous cell population, and is linked to genomic instability. Thus, resumption of the cell cycle a long period after termination in G2 phase can give rise to multiple cell fates. This shifts our current perception of the long-term consequences of cell cycle termination in G2 phase, from a singular outcome of senescence to that of multiple cell fates, possibly alluding to a mechanism by which cells can undergo oncogenic transformation. In summary, this thesis highlights the importance of the spatio-temporal regulation of cyclin A2 in modulating Cdk to initiate the mitotic entry network in G2 phase, ensuring welldelineated progression to mitosis. Identifying the function of RPRM in G2 phase adds to our limited understanding of cell cycle regulation in relation to CHH. Moreover, this thesis reveals that DNA damage-induced cell cycle termination in G2 phase can lead to cell fates other than senescence, an implication that could have relevance in tumourigenesis.
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| 31. |
- Middleton, Anna, et al.
(författare)
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'Your DNA, Your Say': global survey gathering attitudes toward genomics : design, delivery and methods
- 2018
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Ingår i: Personalized Medicine. - : Future Medicine Ltd. - 1741-0541 .- 1744-828X. ; 15:4, s. 311-318
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Tidskriftsartikel (refereegranskat)abstract
- Our international study, 'Your DNA, Your Say', uses film and an online cross-sectional survey to gather public attitudes toward the donation, access and sharing of DNA information. We describe the methodological approach used to create an engaging and bespoke survey, suitable for translation into many different languages. We address some of the particular challenges in designing a survey on the subject of genomics. In order to understand the significance of a genomic result, researchers and clinicians alike use external databases containing DNA and medical information from thousands of people. We ask how publics would like their 'anonymous' data to be used (or not to be used) and whether they are concerned by the potential risks of reidentification; the results will be used to inform policy.
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| 32. |
- Middleton, Matthew J., et al.
(författare)
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Bright radio emission from an ultraluminous stellar-mass microquasar in M 31
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7431, s. 187-190
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Tidskriftsartikel (refereegranskat)abstract
- A subset of ultraluminous X-ray sources (those with luminosities of less than 10(40) erg s(-1); ref. 1) are thought to be powered by the accretion of gas onto black holes with masses of similar to 5-20M(circle dot), probably by means of an accretion disk(2,3). The X-ray and radio emission are coupled in such Galactic sources; the radio emission originates in a relativistic jet thought to be launched from the innermost regions near the black hole(4,5), with the most powerful emission occurring when the rate of infalling matter approaches a theoretical maximum (the Eddington limit). Only four such maximal sources are known in the Milky Way(6), and the absorption of soft X-rays in the interstellar medium hinders the determination of the causal sequence of events that leads to the ejection of the jet. Here we report radio and X-ray observations of a bright new X-ray source in the nearby galaxy M 31, whose peak luminosity exceeded 10(39) erg s(-1). The radio luminosity is extremely high and shows variability on a timescale of tens of minutes, arguing that the source is highly compact and powered by accretion close to the Eddington limit onto a black hole of stellar mass. Continued radio and X-ray monitoring of such sources should reveal the causal relationship between the accretion flow and the powerful jet emission.
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| 33. |
- Milne, Richard, et al.
(författare)
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Demonstrating trustworthiness when collecting and sharing genomic data : public views across 22 countries
- 2021
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPublic trust is central to the collection of genomic and health data and the sustainability of genomic research. To merit trust, those involved in collecting and sharing data need to demonstrate they are trustworthy. However, it is unclear what measures are most likely to demonstrate this.MethodsWe analyse the ‘Your DNA, Your Say’ online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle- and high-income countries, gathered in 15 languages. We examine how participants perceived the relative value of measures to demonstrate the trustworthiness of those using donated DNA and/or medical information. We examine between-country variation and present a consolidated ranking of measures.ResultsProviding transparent information about who will benefit from data access was the most important measure to increase trust, endorsed by more than 50% of participants across 20 of 22 countries. It was followed by the option to withdraw data and transparency about who is using data and why. Variation was found for the importance of measures, notably information about sanctions for misuse of data—endorsed by 5% in India but almost 60% in Japan. A clustering analysis suggests alignment between some countries in the assessment of specific measures, such as the UK and Canada, Spain and Mexico and Portugal and Brazil. China and Russia are less closely aligned with other countries in terms of the value of the measures presented.ConclusionsOur findings highlight the importance of transparency about data use and about the goals and potential benefits associated with data sharing, including to whom such benefits accrue. They show that members of the public value knowing what benefits accrue from the use of data. The study highlights the importance of locally sensitive measures to increase trust as genomic data sharing continues globally.
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| 34. |
- Milne, Richard, et al.
(författare)
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Return of genomic results does not motivate intent to participate in research for all: Perspectives across 22 countries
- 2022
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 24:5, s. 1120-1129
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of this study was to determine how attitudes toward the return of genomic research results vary internationally. Methods: We analyzed the “Your DNA, Your Say” online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle-, and high-income countries, and these were gathered in 15 languages. We analyzed how participants responded when asked whether return of results (RoR) would motivate their decision to donate DNA or health data. We examined variation across the study countries and compared the responses of participants from other countries with those from the United States, which has been the subject of the majority of research on return of genomic results to date. Results: There was substantial variation in the extent to which respondents reported being influenced by RoR. However, only respondents from Russia were more influenced than those from the United States, and respondents from 20 countries had lower odds of being partially or wholly influenced than those from the United States. Conclusion: There is substantial international variation in the extent to which the RoR may motivate people's intent to donate DNA or health data. The United States may not be a clear indicator of global attitudes. Participants’ preferences for return of genomic results globally should be considered.
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| 35. |
- Milne, Richard, et al.
(författare)
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Trust in genomic data sharing among members of the general public in the UK, USA, Canada and Australia
- 2019
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 138:11-12, s. 1237-1246
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Tidskriftsartikel (refereegranskat)abstract
- Trust may be important in shaping public attitudes to genetics and intentions to participate in genomics research and big data initiatives. As such, we examined trust in data sharing among the general public. A cross-sectional online survey collected responses from representative publics in the USA, Canada, UK and Australia (n = 8967). Participants were most likely to trust their medical doctor and less likely to trust other entities named. Company researchers were least likely to be trusted. Low, Variable and High Trust classes were defined using latent class analysis. Members of the High Trust class were more likely to be under 50 years, male, with children, hold religious beliefs, have personal experience of genetics and be from the USA. They were most likely to be willing to donate their genomic and health data for clinical and research uses. The Low Trust class were less reassured than other respondents by laws preventing exploitation of donated information. Variation in trust, its relation to areas of concern about the use of genomic data and potential of legislation are considered. These findings have relevance for efforts to expand genomic medicine and data sharing beyond those with personal experience of genetics or research participants.
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| 36. |
- Nicholas, Richard, et al.
(författare)
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The impact of healthcare systems on the clinical diagnosis and disease-modifying treatment usage in relapse-onset multiple sclerosis : a real-world perspective in five registries across Europe
- 2023
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Ingår i: Therapeutic advances in neurological disorders. - : SAGE Publications. - 1756-2856. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Prescribing guidance for disease-modifying treatment (DMT) in multiple sclerosis (MS) is centred on a clinical diagnosis of relapsing–remitting MS (RRMS). DMT prescription guidelines and monitoring vary across countries. Standardising the approach to diagnosis of disease course, for example, assigning RRMS or secondary progressive MS (SPMS) diagnoses, allows examination of the impact of health system characteristics on the stated clinical diagnosis and treatment access. Methods: We analysed registry data from six cohorts in five countries (Czech Republic, Denmark, Germany, Sweden and United Kingdom) on patients with an initial diagnosis of RRMS. We standardised our approach utilising a pre-existing algorithm (DecisionTree, DT) to determine patient diagnoses of RRMS or secondary progressive MS (SPMS). We identified five global drivers of DMT prescribing: Provision, Availability, Funding, Monitoring and Audit, data were analysed against these concepts using meta-analysis and univariate meta-regression. Results: In 64,235 patients, we found variations in DMT use between countries, with higher usage in RRMS and lower usage in SPMS, with correspondingly lower usage in the UK compared to other registers. Factors such as female gender (p = 0.041), increasing disability via Expanded Disability Status Scale (EDSS) score (p = 0.004), and the presence of monitoring (p = 0.029) in SPMS influenced the likelihood of receiving DMTs. Standardising the diagnosis revealed differences in reclassification rates from clinical RRMS to DT-SPMS, with Sweden having the lowest rate Sweden (Sweden 0.009, range: Denmark 0.103 – UK portal 0.311). Those with higher EDSS at index (p < 0.03) and female gender (p < 0.049) were more likely to be reclassified from RRMS to DT-SPMS. The study also explored the impact of diagnosis on DMT usage in clinical SPMS, finding that the prescribing environment and auditing practices affected access to treatment. Discussion: This highlights the importance of a healthcare system’s approach to verifying the clinical label of MS course in facilitating appropriate prescribing, with some flexibility allowed in uncertain cases to ensure continued access to treatment.
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| 37. |
- Riegel, Barbara, et al.
(författare)
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Self-care research : Where are we now? Where are we going?
- 2021
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Ingår i: International Journal of Nursing Studies. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0020-7489 .- 1873-491X. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: The beneficial effects of self-care include improved well-being and lower morbidity, mortality, and healthcare costs. In this article we address the current state of self-care research and propose an agenda for future research based on the inaugural conference of the International Center for Self-Care Research held in Rome, Italy in June 2019. The vision of this Center is a world where self-care is prioritized by individuals, families, and communities and is the first line of approach in every health care encounter. The mission of the Center is to lead the self-care research endeavor, improving conceptual clarity and promoting interdisciplinary work informed by a shared vision addressing knowledge gaps. A focused research agenda can deepen our theoretical understanding of self-care and the mechanisms underlying self-care, which can contribute to the development of effective interventions that improve outcomes. Methods: During conference discussions, we identified seven major reasons why self-care is challenging, which can be grouped into the general categories of behavior change and illness related factors. We identified six specific knowledge gaps that, if addressed, may help to address these challenges: the influence of habit formation on behavior change, resilience in the face of stressful life events that interfere with self-care, the influence of culture on self-care behavioral choices, the difficulty performing self-care with multiple chronic conditions, self-care in persons with severe mental illness, and the influence of others (care partners, family, peer supporters, and healthcare professionals) on self-care. Plans to achieve results: To achieve the vision and mission of the Center, we will lead a collaborative program of research that addresses self-care knowledge gaps and improves outcomes, create a supportive international network for knowledge transfer and support of innovations in self-care research, and support and train others in self-care research. Beyond these specific short-term goals, important policy implications of this work are discussed. (c) 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
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| 38. |
- Riso, Lukas, et al.
(författare)
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General and abdominal adiposity and the risk of Parkinson's disease : A prospective cohort study
- 2019
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Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 62, s. 98-104
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Due to demographic change, an increase in the frequency of Parkinson's disease (PD) patients is expected in the future and, thus, the identification of modifiable risk factors is urgently needed. We aimed to examine the associations of body mass index (BMI) and waist circumference (WC) with incident PD. Methods: In 13 of the 23 centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a total of 734 incident cases of PD were identified between 1992 and 2012 with a mean follow-up of 12 years. Cox proportional hazards regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). We modelled anthropometric variables as continuous and categorical exposures and performed subgroup analyses by potential effect modifiers including sex and smoking. Results: We found no association between BMI, WC and incident PD, neither among men nor among women. Among never and former smokers, BMI and waist circumference were also not associated with PD risk. For male smokers, however, we observed a statistically significant inverse association between BMI and PD risk (HR 0.51, 95%CI: 0.30, 0.84) and the opposite for women, i.e. a significant direct association of BMI (HR 1.79, 95%CI: 1.04, 3.08) and waist circumference (HR 1.64, 95%CI: 1.03, 2.61) with risk of PD. Conclusion: Our data revealed no association between excess weight and PD risk but a possible interaction between anthropometry, sex and smoking.
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| 39. |
- Sohlenius-Sternbeck, Anna-Karin, et al.
(författare)
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Practical use of the regression offset approach for the prediction of in vivo intrinsic clearance from hepatocytes
- 2012
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Ingår i: Xenobiotica. - : Informa UK Limited. - 0049-8254 .- 1366-5928. ; 42:9, s. 841-853
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Tidskriftsartikel (refereegranskat)abstract
- 1. Systematic under-prediction of clearance is frequently associated with in vitro kinetic data when extrapolated using physiological scaling factors, appropriate binding parameters and the well-stirred model. The present study describes a method of removing this systematic bias through application of empirical correction factors derived from regression analyses applied to the in vitro and in vivo data for a defined set of reference compounds.2. Linear regression lines were established with in vivo intrinsic clearance (CLint), derived from in vivo clearance data and scaled in vitro intrinsic clearance from isolated hepatocyte incubations. The scaled CLint was empirically corrected to a predicted in vivo CLint using the slope and intercept from a uniform weighted linear regression applied to the in vitro to in vivo extrapolation.3. Cross validation of human data demonstrated that 66% of the reference compounds had a predicted in vivo CLint within two-fold of the observed value. The average absolute fold error (AAFE) for the in vivo CLint predictions was 1.90. For rat, 54% of the compounds had a predicted value within two-fold of the observed and the AAFE was 1.98.4. Three AstraZeneca projects are used to exemplify how a two-sided prediction interval, applied to the rat regression corrected reference data, can form the basis for assessing the likelihood that, for a given chemical series, the in vitro kinetic data is predictive of in vivo clearance and is therefore appropriate to guide optimisation of compound metabolic stability.
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| 40. |
- Solé, Carla, et al.
(författare)
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The Circulating Transcriptome as a Source of Biomarkers for Melanoma
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The circulating transcriptome is a valuable source of cancer biomarkers, which, with the exception of microRNAs (miRNAs), remains relatively unexplored. To elucidate which RNAs are present in plasma from melanoma patients and which could be used to distinguish cancer patients from healthy individuals, we used next generation sequencing (NGS), and validation was carried out by qPCR and/or ddPCR. We identified 442 different microRNAs in samples, eleven of which were differentially expressed (p < 0.05). Levels of miR-134-5p and miR-320a-3p were significantly down-regulated (p < 0.001) in melanoma samples (n = 96) compared to healthy controls (n = 28). Differentially expressed protein-encoding mRNA 5 '-fragments were enriched for the angiopoietin, p21-activated kinase (PAK), and EIF2 pathways. Levels of ATM1, AMFR, SOS1, and CD109 gene fragments were up-regulated (p < 0.001) in melanoma samples (n = 144) compared to healthy controls (n = 41) (AUC = 0.825). Over 40% of mapped reads were YRNAs, a class of non-coding RNAs that to date has been little explored. Expression levels of RNY3P1, RNY4P1, and RNY4P25 were significantly higher in patients with stage 0 disease than either healthy controls or more advanced stage disease (p < 0.001). In conclusion, we have identified a number of novel RNA biomarkers, which, most importantly, we validated in multi-center retrospective and prospective cohorts, suggesting potential diagnostic use of these RNA species.
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| 41. |
- Tinetti, G., et al.
(författare)
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A chemical survey of exoplanets with ARIEL
- 2018
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
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| 42. |
- Tinetti, Giovanna, et al.
(författare)
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The EChO science case
- 2015
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of almost two thousand exoplanets has revealed an unexpectedly diverse planet population. We see gas giants in few-day orbits, whole multi-planet systems within the orbit of Mercury, and new populations of planets with masses between that of the Earth and Neptune-all unknown in the Solar System. Observations to date have shown that our Solar System is certainly not representative of the general population of planets in our Milky Way. The key science questions that urgently need addressing are therefore: What are exoplanets made of? Why are planets as they are? How do planetary systems work and what causes the exceptional diversity observed as compared to the Solar System? The EChO (Exoplanet Characterisation Observatory) space mission was conceived to take up the challenge to explain this diversity in terms of formation, evolution, internal structure and planet and atmospheric composition. This requires in-depth spectroscopic knowledge of the atmospheres of a large and well-defined planet sample for which precise physical, chemical and dynamical information can be obtained. In order to fulfil this ambitious scientific program, EChO was designed as a dedicated survey mission for transit and eclipse spectroscopy capable of observing a large, diverse and well-defined planet sample within its 4-year mission lifetime. The transit and eclipse spectroscopy method, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allows us to measure atmospheric signals from the planet at levels of at least 10(-4) relative to the star. This can only be achieved in conjunction with a carefully designed stable payload and satellite platform. It is also necessary to provide broad instantaneous wavelength coverage to detect as many molecular species as possible, to probe the thermal structure of the planetary atmospheres and to correct for the contaminating effects of the stellar photosphere. This requires wavelength coverage of at least 0.55 to 11 mu m with a goal of covering from 0.4 to 16 mu m. Only modest spectral resolving power is needed, with R similar to 300 for wavelengths less than 5 mu m and R similar to 30 for wavelengths greater than this. The transit spectroscopy technique means that no spatial resolution is required. A telescope collecting area of about 1 m(2) is sufficiently large to achieve the necessary spectro-photometric precision: for the Phase A study a 1.13 m(2) telescope, diffraction limited at 3 mu m has been adopted. Placing the satellite at L2 provides a cold and stable thermal environment as well as a large field of regard to allow efficient time-critical observation of targets randomly distributed over the sky. EChO has been conceived to achieve a single goal: exoplanet spectroscopy. The spectral coverage and signal-to-noise to be achieved by EChO, thanks to its high stability and dedicated design, would be a game changer by allowing atmospheric composition to be measured with unparalleled exactness: at least a factor 10 more precise and a factor 10 to 1000 more accurate than current observations. This would enable the detection of molecular abundances three orders of magnitude lower than currently possible and a fourfold increase from the handful of molecules detected to date. Combining these data with estimates of planetary bulk compositions from accurate measurements of their radii and masses would allow degeneracies associated with planetary interior modelling to be broken, giving unique insight into the interior structure and elemental abundances of these alien worlds. EChO would allow scientists to study exoplanets both as a population and as individuals. The mission can target super-Earths, Neptune-like, and Jupiter-like planets, in the very hot to temperate zones (planet temperatures of 300-3000 K) of F to M-type host stars. The EChO core science would be delivered by a three-tier survey. The EChO Chemical Census: This is a broad survey of a few-hundred exoplanets, which allows us to explore the spectroscopic and chemical diversity of the exoplanet population as a whole. The EChO Origin: This is a deep survey of a subsample of tens of exoplanets for which significantly higher signal to noise and spectral resolution spectra can be obtained to explain the origin of the exoplanet diversity (such as formation mechanisms, chemical processes, atmospheric escape). The EChO Rosetta Stones: This is an ultra-high accuracy survey targeting a subsample of select exoplanets. These will be the bright "benchmark" cases for which a large number of measurements would be taken to explore temporal variations, and to obtain two and three dimensional spatial information on the atmospheric conditions through eclipse-mapping techniques. If EChO were launched today, the exoplanets currently observed are sufficient to provide a large and diverse sample. The Chemical Census survey would consist of > 160 exoplanets with a range of planetary sizes, temperatures, orbital parameters and stellar host properties. Additionally, over the next 10 years, several new ground- and space-based transit photometric surveys and missions will come on-line (e.g. NGTS, CHEOPS, TESS, PLATO), which will specifically focus on finding bright, nearby systems. The current rapid rate of discovery would allow the target list to be further optimised in the years prior to EChO's launch and enable the atmospheric characterisation of hundreds of planets.
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| 43. |
- Voigt, Torsten H, et al.
(författare)
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Willingness to donate genomic and other medical data: results from Germany
- 2020
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Ingår i: European Journal of Human Genetics. - : Springer Nature. - 1018-4813 .- 1476-5438. ; 28:8, s. 1000-1009
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports findings from Germany-based participants in the "Your DNA, Your Say" study, a collaborative effort among researchers in more than 20 countries across the world to explore public attitudes, values and opinions towards willingness to donate genomic and other personal data for use by others. Based on a representative sample of German residents (n = 1506) who completed the German-language version of the survey, we found that views of genetic exceptionalism were less prevalent in the German-language arm of the study than in the English-language arm (43% versus 52%). Also, people's willingness to make their data available for research was lower in the German than in the English-language samples of the study (56% versus 67%). In the German sample, those who were more familiar with genetics, and those holding views of genetic exceptionalism were more likely to be willing to donate data than others. We explain these findings with reference to the important role that the "right of informational self-determination" plays in German public discourse. Rather than being a particularly strict interpretation of privacy in the sense of a right to be left alone, the German understanding of informational self-determination bestows on each citizen the responsibility to carefully consider how their personal data should be used to protect important rights and to serve the public good.
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| 44. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813 .- 1089-490X. ; 92:3
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Tidskriftsartikel (refereegranskat)
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| 45. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :8
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Tidskriftsartikel (refereegranskat)
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| 46. |
- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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